Hyperthyroidism can cause glucose metabolism disorders and insulin resistance. Insulin resistance in muscle and adipose tissues has been extensively studied, whereas investigations on β-cell insulin resistance are limited. This study preliminarily explored the effects of high T3 levels on β-cell line (MIN6) insulin resistance, as well as the roles of endoplasmic reticulum stress (ERS). In this study, we treated β-cell line with T3, with or without an inhibitor of phosphotyrosine phosphatases (PTPs, sodium vanadate) or ERS inhibitor (4-PBA). The results indicated that high levels of T3 significantly inhibited insulin secretion in β-cell line. In addition, we observed an upregulation of p-IRS-1^ser307 and downregulation of Akt. These results can be corrected by sodium vanadate. Moreover, high T3 levels upregulate the ERS-related proteins PERK, IRE1, ATF6, and GRP78, as well as ERS-related apoptosis CHOP and caspase-12. Similarly, this change can be corrected by 4-PBA. These results suggest that high T3 levels can induce insulin resistance in β-cell line by activating ERS and the apoptotic pathway.

中文翻译：

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高T3通过内质网应激诱导β细胞胰岛素抵抗。

甲状腺功能亢进会引起葡萄糖代谢异常和胰岛素抵抗。肌肉和脂肪组织中的胰岛素抵抗已被广泛研究，而对β细胞胰岛素抵抗的研究却很有限。这项研究初步探讨了高T3水平对β细胞系（MIN6）胰岛素抵抗的影响，以及内质网应激（ERS）的作用。在这项研究中，我们用T3处理β细胞系，使用或不使用磷酸酪氨酸磷酸酶抑制剂（PTP，钒酸钠）或ERS抑制剂（4-PBA）。结果表明高水平的T3显着抑制β细胞系中的胰岛素分泌。此外，我们观察到p-IRS-1 ^ser307的上调和Akt的下调。这些结果可以用钒酸钠校正。此外，高T3水平会上调ERS相关蛋白PERK，IRE1，ATF6和GRP78，以及ERS相关凋亡CHOP和caspase-12。同样，可以通过4-PBA纠正此更改。这些结果表明高水平的T3可以通过激活ERS和凋亡途径来诱导β细胞系中的胰岛素抵抗。